Primary isoniazid prophylaxis against tuberculosis in HIV-exposed children.
Primary isoniazid prophylaxis against tuberculosis in HIV-exposed children.
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DOI：
10.1056/nejmoa1011214
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发表时间：
2011-07-07
期刊：
影响因子：
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通讯作者：
P1041 Study Team
中科院分区：
文献类型：
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作者：
Madhi SA;Nachman S;Violari A;Kim S;Cotton MF;Bobat R;Jean-Philippe P;McSherry G;Mitchell C;P1041 Study Team
人体免疫机能丧失病毒（艾滋病毒）和结核病的双重流行病是撒哈拉以南非洲疾病和死亡的主要原因。我们进行了一项双盲、随机、安慰剂对照试验，在围产期暴露于HIV的HIV感染儿童和未感染儿童中，对暴露前异烟肼预防结核病进行了研究。我们将548名HIV感染婴儿和804名未感染HIV的婴儿（91至120天）随机分配给异烟肼（每天每公斤体重10至20毫克）或匹配的安慰剂，为期96周。所有患者在出生后30天内接受了卡介苗（BCG）结核病疫苗接种。感染艾滋病毒的儿童可以获得抗逆转录病毒疗法。主要结局指标为随机分组后96 - 108周内HIV感染儿童的结核病和死亡以及HIV未感染儿童的潜伏性结核感染、结核病和死亡。研究期间，98.9%的艾滋病毒感染儿童开始接受抗逆转录病毒治疗。在HIV感染儿童中，异烟肼组52名（19.0%）和安慰剂组53名（19.3%）发生了方案定义的结核病或死亡（P = 0.93）。在未感染HIV的儿童中，异烟肼组（39名儿童，10%）和安慰剂组（45名儿童，11%; P = 0.44）的结核感染、结核病或死亡的合并发生率无显著差异。艾滋病毒感染儿童的结核病发病率为121例/1000儿童年（95%置信区间[CI]，95 - 153），而未感染艾滋病毒儿童的结核病发病率为41例/1000儿童年（95% CI，31 - 52）。治疗组之间的临床或重度实验室毒性反应无显著差异。一级异烟肼预防并不能提高HIV感染儿童的无结核病生存率，也不能提高接种BCG疫苗的未感染HIV儿童的无结核病生存率。尽管可以获得抗逆转录病毒疗法，但感染艾滋病毒的儿童的结核病负担仍然很重。（由美国国立卫生研究院和安全未来资助; ClinicalTrials.gov编号，NCT 00080119。
The dual epidemic of human immunodeficiency virus (HIV) and tuberculosis is a major cause of sickness and death in sub-Saharan Africa. We conducted a double-blind, randomized, placebo-controlled trial of preexposure isoniazid prophylaxis against tuberculosis in HIV-infected children and uninfected children exposed to HIV during the perinatal period. We randomly assigned 548 HIV-infected and 804 HIV-uninfected infants (91 to 120 days of age) to isoniazid (10 to 20 mg per kilogram of body weight per day) or matching placebo for 96 weeks. All patients received bacille Calmette–Guérin (BCG) vaccination against tuberculosis within 30 days after birth. HIV-infected children had access to antiretroviral therapy. The primary outcome measures were tuberculosis disease and death in HIV-infected children and latent tuberculosis infection, tuberculosis disease, and death in HIV-uninfected children within 96 to 108 weeks after randomization. Antiretroviral therapy was initiated in 98.9% of HIV-infected children during the study. Among HIV-infected children, protocol-defined tuberculosis or death occurred in 52 children (19.0%) in the isoniazid group and 53 (19.3%) in the placebo group (P = 0.93). Among HIV-uninfected children, there was no significant difference in the combined incidence of tuberculosis infection, tuberculosis disease, or death between the isoniazid group (39 children, 10%) and the placebo group (45 children, 11%; P = 0.44). The rate of tuberculosis was 121 cases per 1000 child-years (95% confidence interval [CI], 95 to 153) among HIV-infected children as compared with 41 per 1000 child-years (95% CI, 31 to 52) among HIV-uninfected children. There were no significant differences in clinical or severe laboratory toxic effects between treatment groups. Primary isoniazid prophylaxis did not improve tuberculosis-disease–free survival among HIV-infected children or tuberculosis-infection–free survival among HIV-uninfected children immunized with BCG vaccine. Despite access to antiretroviral therapy, the burden of tuberculosis remained high among HIV-infected children. (Funded by the National Institutes of Health and Secure the Future; ClinicalTrials.gov number, NCT00080119.)